OBJECTIVES: To assess the value for money of introducing three-drug antiretroviral regimens, namely 1) zidovudine--AZT, lamivudine--3TC, and efavirenz--EFV; or 2) AZT, 3TC and lopinavir/ritonavir--LPV/r, in comparison to the current protocol, AZT plus single-dose nevirapine--sd-NVP, for the prevention of mother-to-child transmission (PMTCT) of HIV in Thailand.  METHODS: A decision tree was constructed to predict costs and outcomes using the Thai governmental perspective. The costs consisted of 1) program costs, 2) costs of treatment of premature birth, 3) costs of treatment of paediatric HIV infection, and 4) costs of treatment of drug resistance among mothers. All costs were presented in 2009 Thai baht. The outcome was measured in terms of quality-adjusted life years (QALYs) gained from infant HIV infection averted. The costs and outcomes were discounted with the rate of 3% as recommended by the national guidelines.  RESULTS: Introduction of the three-drug antiretroviral regimens yields lower costs and better health outcomes compared to AZT+sd-NVP. Although these three-drug regimens offer higher program costs and health care costs for premature birth, they significantly save money in regard to paediatric HIV treatment and treatment costs for drug resistance in the mothers. In addition, approximately 1 QALY is averted as a result of using the regimens. Because of the lack of clinical evidence to distinguish the difference in terms of PMTCT efficacy between EFV-based and LPV/r-based regimens, the analysis favours a cheaper EFV-based regimen. Results from univariate uncertainty analysis also support the above conclusion and a tornado diagram presents the relative importance of each model input parameter.  CONCLUSIONS: The three-drug regimens are cost-saving for PMTCT in Thailand, and findings from this study support a change in the National PMTCT guidelines in the country.